Effect of Angiotensin II Receptor Blocker on Experimental Periodontitis in a Mouse Model of Marfan Syndrome

Marfan syndrome is an autosomal dominant disease characterized by aneurysm and dilatation of the aortic root, tall stature, and ectopia lentis. These manifestations reflect excessive signaling of transforming growth factor beta (TGF-beta). Moreover, cases are frequently associated with severe periodontitis, which is a chronic inflammation of the gingiva, periodontal ligament, and alveolar bone. Recently, angiotensin II receptor blockers (ARBs) were discovered to be an effective drug class that can prevent aortic aneurysm and dilation in Marfan syndrome by inhibiting TGF-beta signaling. To investigate the effect of ARB on the progression of periodontitis, the application of a potent ARB, telmisartan, was examined in a mouse model of Marfan syndrome (Mg Delta). Six-week-old male heterozygous Mg Delta and wild-type mice were challenged with Porphyromonas gingivalis, which causes chronic periodontitis, with and without telmisartan application. After infection, alveolar bone resorption was measured by micro-computed tomography (mu CT), and inflammatory cytokine levels were examined. Infection of Porphyromonas gingivalis induced alveolar bone resorption in both Mg Delta and wild-type mice. The amount of resorption was significantly larger in the former than the latter. Immunoarray and enzyme-linked immunosorbent assay (ELISA) analyses demonstrated that interleukin-17 (IL-17) and tumor necrosis factor alpha (TNF-alpha) levels were significantly higher in infected Mg Delta mice than infected wild-type mice. Telmisartan treatment significantly suppressed the alveolar bone resorption of infected Mg Delta mice. Telmisartan also significantly decreased levels of TGF-beta, IL-17, and TNF-alpha in infected Mg Delta mice to levels seen in infected wild-type mice. This study suggests that ARB can prevent the severe periodontitis frequently seen in Marfan syndrome.